PubMed Health⌕ Search

Biomedical subjects

Elizabeth Johnson

Publications and source records attributed to Elizabeth Johnson.

36 records · Page 2Linked to original sources
PubMed2004

BRCA1/2 testing in hereditary breast and ovarian cancer families: effectiveness of problem-solving training as a counseling intervention.

It remains uncertain whether members of hereditary breast and ovarian cancer (HBOC) families experience psychological distress with genetic testing and whether pre-test counseling can have a moderating effect on client well-being. One purpose of this study was to assess change in psychological well-being from baseline to 6-9 months follow-up and the effect of a problem-solving training (PST) intervention on psychological well-being. Two hundred and twelve members of 13 HBOC families were offered BRCA1/2 testing for a previously identified family mutation. Participants received education and were randomized to one of two counseling interventions; PST or client-centered counseling. Psychological well-being was assessed at baseline and again at 6-9 months following the receipt of test results, or at the equivalent time for those participants who chose not to undergo testing. Well-being was assessed using measures of depressive symptoms (CESD), intrusive thoughts (IES), cancer worries, and self-esteem. Comparisons were made between those who chose testing and those who did not as well as between those who received positive and negative test results. One hundred eighty one participants elected to undergo genetic testing (85%) and 47 of these (26%) were identified as BRCA1/2 mutation carriers. Breast and ovarian cancer worries decreased significantly (p = 0.007 and 0.008, respectively) in those who tested negative while there was no appreciable change in psychological well-being from baseline to follow-up in either those who tested positive or in non-testers. Among all participants, particularly testers, those randomized to PST had a greater reduction in depressive symptoms than those randomized to client-centered counseling (p < 0.05 and p = 0.02, respectively). Regardless of the decision to test, individuals with a personal history of cancer (n = 22) were more likely to have an increase in breast cancer worries compared to those who had never been diagnosed with cancer (p < 0.001). Results suggest that a problem-solving counseling intervention may help to enhance psychological well-being following testing and that a personal history of cancer may increase psychological distress associated with genetic testing.

Adult↗
PubMed2004

Phase II trial of vinorelbine plus doxorubicin in relapsed small-cell lung cancer: CALGB 9332.

Small-cell lung cancer that progresses after initial response may still be sensitive to systemic treatment. This study assessed doxorubicin plus vinorelbine tartrate (Navelbine Injection) in patients who had no prior exposure to these agents. Treatment consisted of vinorelbine at 25 mg/m2 on days 1 and 8 and doxorubicin at 50 mg/m2 on day 1 of each 21-day cycle. The trial was stopped early because of excessive toxicity. The partial response rate was 26.7%. Toxicities included grade IV neutropenia in 73%, and febrile neutropenia and/or sepsis in 60%. Three patients died from sepsis during cycle 1. Performance status 2 was significantly associated with febrile neutropenia (p = 0.044). Although this regimen had some activity, the toxicity precluded further evaluation.

Adult↗
PubMed2004

Posaconazole therapy of disseminated phaeohyphomycosis in a murine model.

Immunocompetent (nu/+) and athymic (nu/nu) BALB/c mice were infected intravenously with Wangiella dermatitidis and treated with posaconazole. Posaconazole reduced the counts in tissues and prolonged survival. Of particular interest, posaconazole reduced the counts of this neurotropic pathogen in the brain.

Animals↗
PubMed2003

Colinearity of reverse transcriptase inhibitor resistance mutations detected by population-based sequencing.

High-level resistance to multiple drugs is often detected by directly sequencing uncloned polymerase chain reaction products (population-based sequencing). It is not known, however, if this method of identifying mutations gives an accurate picture of individual viral genomes. To determine how often multidrug-resistant isolates consist of clones containing every mutation present in the population-based sequence, a mean of 2.8 molecular clones was sequenced from the plasma of 25 heavily treated persons whose population-based sequence contained multiple reverse transcriptase (RT) inhibitor resistance mutations (71 clones). The 25 population-based sequences contained a mean of 5.7 nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations and 1.2 nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations. The 71 clones contained a mean of 5.3 NRTI resistance mutations and 1.0 NNRTI resistance mutations. Sequences of clones closely resembled the population-based sequence: 36 (51%) clones had each of the RT inhibitor mutations present in the population-based sequence, 25 (35%) had all but 1 RT inhibitor mutation, 4 (6%) had all but 2 RT inhibitor mutations, 3 (4%) had all but 3 RT inhibitor mutations, and 3 (4%) had all but 4 RT inhibitor mutations. Phenotypic testing of 29 clones showed that most clones were resistant to nearly all NRTIs and that those with NNRTI resistance mutations were also resistant to multiple NNRTIs. These data show that in heavily treated persons, most RT inhibitor resistance mutations are present in the same viral genomes (colinear) and that multidrug resistance often occurs within individual clones as well as within virus populations.

Amino Acid Sequence↗
PubMed2003

Mu-opioid receptor desensitization in mature rat neurons: lack of interaction between DAMGO and morphine.

Mu-opioid receptors (MORs) exhibit rapid desensitization and internalization during exposure to various opioid agonists. In some studies, however, morphine has been observed to produce little MOR desensitization or internalization. We examined desensitization in mature rat locus ceruleus (LC) neurons and confirmed that morphine is a very poor desensitizing agent, whereas [D-Ala2,N-MePhe4,Gly-ol5]enkephalin (DAMGO), a high-efficacy agonist, and methadone, an agonist we observed to be of equivalent efficacy to morphine, produced profound rapid desensitization. Similarly, by measuring plasma membrane receptor levels in HEK293 cells stably expressing T7-epitope-tagged rat MOR1 at near physiological levels (HEK293-MOR1 cells), DAMGO and methadone but not morphine caused rapid MOR internalization. It has been reported that a low concentration of DAMGO, coapplied with morphine, caused morphine to induce MOR internalization. We examined whether this interaction occurred in mature mammalian neurons at the level of receptor desensitization. Coapplication of low concentrations of DAMGO did not increase morphine-induced desensitization in LC neurons but caused a lesser degree of desensitization than DAMGO alone. We also failed to observe an enhancement by DAMGO of morphine-induced desensitization in the electrically stimulated guinea pig ileum myenteric plexus-longitudinal muscle preparation. In HEK293-MOR1 cells, low concentrations of DAMGO did not convert morphine into a receptor-internalizing agent. The data presented here fail to support the theory that low concentrations of DAMGO can increase morphine-induced MOR desensitization or internalization.

Analgesics, Opioid↗
PubMed2003

Modeling the optimum duration of antibiotic prophylaxis in an anthrax outbreak.

A critical consideration in effective and measured public health responses to an outbreak of inhalational anthrax is the optimum duration of antibiotic prophylaxis. We develop a competing-risks model to address the duration of antibiotic prophylaxis and the incubation period that accounts for the risks of spore germination and spore clearance. The model predicts the incubation period distribution, which is confirmed by empirical data. The optimum duration of antibiotic prophylaxis depends critically on the dose of inhaled spores. At high doses, we show that exposed persons would need to remain on antibiotic prophylaxis for at least 4 months, and considerable morbidity would likely occur before antibiotic prophylaxis could even be initiated. At very low doses, 60 days of antibiotic prophylaxis is adequate. Exposure doses can be estimated from the cumulative attack rate up to the point antibiotic prophylaxis begins. The model explains that whereas < or =60 days of antibiotics were enough to protect persons in the 2001 U.S. outbreak, because doses were very low, at moderate or high doses considerably longer durations would be necessary to adequately protect exposed populations.

Anthrax↗
PubMed2003

Voriconazole treatment for less-common, emerging, or refractory fungal infections.

Treatments for invasive fungal infections remain unsatisfactory. We evaluated the efficacy, tolerability, and safety of voriconazole as salvage treatment for 273 patients with refractory and intolerant-to-treatment fungal infections and as primary treatment for 28 patients with infections for which there is no approved therapy. Voriconazole was associated with satisfactory global responses in 50% of the overall cohort; specifically, successful outcomes were observed in 47% of patients whose infections failed to respond to previous antifungal therapy and in 68% of patients whose infections have no approved antifungal therapy. In this population at high risk for treatment failure, the efficacy rates for voriconazole were 43.7% for aspergillosis, 57.5% for candidiasis, 38.9% for cryptococcosis, 45.5% for fusariosis, and 30% for scedosporiosis. Voriconazole was well tolerated, and treatment-related discontinuations of therapy or dose reductions occurred for <10% of patients. Voriconazole is an effective and well-tolerated treatment for refractory or less-common invasive fungal infections.

Adolescent↗
PubMed2003

Patient preferences for eye drop characteristics: a willingness-to-pay analysis.

OBJECTIVE: To determine the importance that patients place on the characteristics of topical therapy for lowering intraocular pressure. METHODS: We administered a willingness-to-pay instrument to 230 patients from 4 glaucoma subspecialty practices, asking them how much they would be willing to pay to obtain particular characteristics in an eye drop. Data about the subjects' demographics, economic status, attitudes toward eye drops and systemic medications, and symptoms from eye drops were correlated with their willingness to pay using 2-part models. RESULTS: Of our subjects, 169 (77%) were using eye drops to lower their intraocular pressure. Fatigue, blurred vision, and tearing were the most commonly reported symptoms. Eye drop medications most valued by the subjects did not produce blurring, drowsiness, or inhibition of sexual performance; 85% were willing to pay more for an eye drop that did not cause blurring, and on average they were willing to pay 40% more. Higher educational levels and income were generally associated with a willingness to pay more for eye drops with desirable attributes. MAIN OUTCOME MEASURE: Willingness to pay more (in dollars). CONCLUSIONS: Patient preferences for eye drop characteristics can be assessed using a willingness-to-pay instrument. Patients place differing value on various eye drop characteristics. A better understanding of patient preference could lead to better compliance.

Aged↗
PubMed2003

Understanding hospital readiness for computerized physician order entry.

BACKGROUND: Many hospitals in the United States are in early stages of decision making and planning to implement computerized physician order entry (CPOE) to improve patient safety and quality of care. The targeted processes and the software for CPOE are complex, and implementation is a large-scale change effort for most hospitals. Hospitals can increase the likelihood of success by understanding and addressing gaps in CPOE readiness. ASSESSING CPOE READINESS: A CPOE readiness assessment tool was developed that includes several different components: external environment; organizational leadership, structure, and culture; care standardization;, order management; access to information; information technology composition; and infrastructure. The presence or absence of these indicators in a particular hospital was determined by on-site interviews, walkarounds with direct observations, and document review. RESULTS: Assessment results for the first 17 hospitals (bed size, 75-906 beds) indicated that the lowest average component score was in care standardization, while the highest average component score was in organizational structure and function. Organizational culture and the order management process also had low average scores. CONCLUSIONS: This CPOE readiness assessment revealed significant gaps in all the hospitals examined. Identifying these gaps and addressing them before CPOE implementation can reduce risks. Organizations need to develop expertise at accomplishing and sustaining change; understanding and building CPOE readiness is an important first step.

Attitude of Health Personnel↗
PubMed2003

The descent curve of the grand multiparous woman.

OBJECTIVE: The purpose of this study was to compare the descent curves and second-stage length among grand multiparous, nulliparous, and lower parity multiparous women. STUDY DESIGN: Retrospective cohorts of spontaneously laboring, vertex-presenting, term, grand multiparous women (parity >or=5) from two medical centers over 5.5 years were matched randomly to nulliparous women and lower parity multiparous women controlled for age, hospital, and year of delivery. Descent curves were modeled from serial cervical examination data by the estimation of the probability of a given station occurring at a given time before delivery with the use of ordinal logistic regression. Curves were compared by Wald tests and adjusted for possible confounders. Second-stage lengths were compared by a Cox proportional hazards model. A probability value of <.05 was considered significant. RESULTS: Grand multiparous women and lower parity multiparous women maintain a high station up to 1.5 hour before delivery and then rapidly transition to delivery. Nulliparous women transition to lower stations at a more gradual rate throughout the first and second stages. Descent curves differ among parity groups, with grand multiparous women maintaining a higher station for a longer time compared with either lower parity multiparous women or nulliparous women (P<.001). Once full dilation is reached, the median length of the second stage is 0.75, 0.85, and 1.75 hours for grand multiparous women, lower parity multiparous women, and nulliparous women, respectively (hazard ratios were 0.39 for nulliparous women vs grand multiparous women and 0.9 for lower parity multiparous women vs grand multiparous women). CONCLUSIONS: Compared with lower parity multiparous women or nulliparous women, grand multiparous women maintain a higher station for a longer time before delivery but transition rapidly to delivery once full dilation is reached.

Adult↗
PubMed2003

Mortality and morbidity in laboratory-maintained Rhesus monkeys and effects of long-term dietary restriction.

Mortality and morbidity were examined in 117 laboratory-maintained rhesus monkeys studied over approximately 25 years (8 dietary-restricted [DR] and 109 ad libitum-fed [AL] monkeys). During the study, 49 AL monkeys and 3 DR monkeys died. Compared with the DR monkeys, the AL monkeys had a 2.6-fold increased risk of death. Hyperinsulinemia led to a 3.7-fold increased risk of death (p <.05); concordantly, the risk of death decreased by 7%, per unit increase in insulin sensitivity (M). There was significant organ pathology in the AL at death. The age at median survival in the AL was approximately 25 years compared with 32 years in the DR. The oldest monkey was a diabetic female (AL) that lived to be 40 years of age. These results suggest that dietary restriction leads to an increased average age of death in primates, associated with the prevention of hyperinsulinemia and the mitigation of age-related disease.

Animals↗
PubMed2002

A home-based nutrition intervention to increase consumption of fruits, vegetables, and calcium-rich foods in community dwelling elders.

OBJECTIVE: To increase fruit, vegetable, and calcium-rich food consumption in community-dwelling, functionally impaired elderly. DESIGN: Six-month, home-based nutrition intervention study. SUBJECTS: Seventy men and women older than age 69 years were randomized to either a nutrition education intervention (n = 38) or a control group that received an exercise intervention (n = 32). INTERVENTION: Nutrition education was designed to increase fruit, vegetable, and calcium-rich food consumption. MAIN OUTCOME MEASURES: Food intake was assessed by a food frequency questionnaire. Fasting blood measures of nutrients and carotenoids were performed. Statistical Analysis Two-group randomized controlled trial with pre-test and post-test design and intention-to-treat analysis. Analysis of covariance to was used to assess differences between the two groups. Baseline and change partial correlation coefficients were performed between intake and blood nutrient levels. Paired t tests were conducted to test within-group changes. RESULTS: Compared with the exercise group, subjects in nutrition group increased their self-reported intake of fruits by 1.1 +/- 0.2 (mean +/- SEM) servings per day (2.8 to 3.9, P = .01), vegetables 1.1 +/- 0.2 servings per day (2.3 to 3.4, P = .001), and milk/dairy 0.9 +/- 0.2 servings per day (3.0 to 3.9, P = .001). There was an increase in the dietary intake of alpha-carotene and beta-carotene in the nutrition group and this correlated with the increase in blood concentrations of alpha-carotene and beta-carotene (P < or = .02; r = 0.33 and r = 0.33, respectively). CONCLUSION: The results of this study suggest that it is possible to improve the dietary intake of community dwelling elders to include more fruits, vegetables, and calcium-rich foods. Recommendations for increasing consumption of fruits, vegetables, and calcium-rich foods should be specific and individualized to meet the dietary pattern and lifestyle of the individual. Compliance should be encouraged with record keeping as well as through continuous monitoring and positive reinforcement.

Aged↗
PubMed2002

Remission and survival following monthly intraarterial cisplatinum in nonresectable hepatoma.

PRECIS: Intraarterial delivery of 50 mg/m2 cisplatinum on a monthly basis is a well-tolerated regimen for patients with nonresectable hepatoma. The selective uptake of cisplatinum delivered intraarterially suggests other selective intraarterial protocols would be of use in regional cancers treated with cisplatinum. BACKGROUND: Sixty-seven patients with nonresectable hepatoma were treated with hepatic artery infusions (HAI) of 50 mg/m2 cisplatinum on a monthly basis. METHODS: Forty-eight patients received an initial course of whole liver external radiation with intravenous (i.v.) cisplatinum 50 mg/m2. Nineteen patients did not receive radiation and received HAI cisplatinum only. All patients then received HAI cisplatinum at 50 mg/m2 on a monthly basis. Six patients were given a tracer dose of radioactive 195m cisplatinum for quantitation by the HAI and i.v. routes. RESULTS: Monthly HAI cisplatinum was well tolerated and could be repeated indefinitely. Median survival for primarily treated nonresectable hepatomas was 12 months [alpha fetoprotein (AFP) elevated] and 17.5 months (AFP negative). Radioactive cisplatinum given by HAI yielded 34-55% tumor uptake of cisplatinum vs. < 5% by i.v. delivery. CONCLUSIONS: Hepatic intraarterial cisplatinum at 50 mg/m2 is a well-tolerated monthly regimen for patients with nonresectable hepatoma.

Adult↗
PubMed2002

Why do children become vitamin A deficient?

Vitamin A deficiency is very prevalent and contributes substantially to morbidity and mortality among young children in developing countries. We identify and quantify three causes of vitamin A deficiency in young children based on data available in the literature: maternal vitamin A deficiency resulting in low concentrations of vitamin A in breast milk, inadequate dietary intake of vitamin A during and after weaning and prevalent illness. We developed a set of recursive equations to estimate the amount of vitamin A in the liver as a function of age over the first 2 y of life. To apply the equations, we selected a best estimate value for each input parameter as the most representative of a typical child in a developing country. Because of the great variability that exists for each variable, we also carried out sensitivity analyses, substituting more extreme values for input parameters. We then estimated stores, assuming a child in a developing country also receives the newly revised vitamin A supplementation regimen recommended by the World Health Organization. Without supplementation, a typical child in a developing country is not able to attain and maintain "minimally adequate" liver vitamin A stores. To overcome this deficit by eating fruits and vegetables alone, the child would need to increase portion sizes about 10-fold. If the child receives the new supplementation regimen, his or her liver stores will still be far short of the average American child (i.e., exceedingly far from toxic levels). However, our estimates indicate that the new supplementation regimen will permit a typical child in a developing country setting to attain minimally adequate vitamin A stores during the first 2 y of life.

Bangladesh↗
PubMed2002

Pilot study of antibiotic cycling in a pediatric intensive care unit.

OBJECTIVE: This pilot study was performed to determine the safety and size of effect of antibiotic cycling to reduce colonization and infection with antibiotic-resistant bacteria. DESIGN: Open, observational study. SETTING: The study was performed in a 16-bed pediatric medical-surgical intensive care unit. PATIENTS: Critically ill children requiring antibiotic therapy. INTERVENTIONS: Three antibiotic classes were systematically cycled for 3-month intervals over 18 months. Antibiotic regimens were used for all empirical therapy and continued if the bacterial isolate was susceptible. MEASUREMENTS: The primary outcome was colonization with antibiotic-resistant bacteria, determined by surveillance cultures obtained twice monthly from all patients in the unit. Rates of antibiotic-resistant, nosocomial blood stream infections, and risks of colonization over calendar time in the intensive care unit were also evaluated. MAIN RESULTS: The cycling of broad-spectrum, empirical antibiotics was safe and did not generate increased antibiotic resistance nor select for new organisms. Over the study period, the trend in prevalence of children colonized with antibiotic-resistant bacteria was from 29% to 24% (p =.41). The effect on prevalence of resistant blood stream infections was similar (p =.29). Changes in individual risks of colonization with resistant bacteria over calendar time were consistent with the ecologic effect in size and direction. CONCLUSIONS: Results of this pilot intervention suggest that cycling antibiotics may be a safe and viable strategy to minimize the emergence of antibiotic resistance in intensive care units. A definitive study will require a randomized and controlled trial of only four pediatric intensive care units over an 18-month period.

Anti-Bacterial Agents↗
PubMed2002

External quality assessment program for Chlamydia trachomatis diagnostic testing by nucleic acid amplification assays.

We report the results from 57 Australian diagnostic laboratories testing two external quality assessment panels using either the Roche Amplicor Chlamydia trachomatis test (R-PCR) or the Abbott LCx Chlamydia trachomatis assay (A-ligase chain reaction [LCR]). Panel samples were either normal urine spiked with Chlamydia trachomatis antigen or clinical urine specimens. There was no significant difference between laboratories or between assays in detection of C. trachomatis-positive clinical samples. Only at the lower limit of detection of the assays did the R-PCR demonstrate increased sensitivity over the A-LCR in the detection of C. trachomatis antigen. However, it was found that single-sample testing could lead to decreased test sensitivity. Detection of the presence of inhibitors of nucleic acid amplification differed between laboratories.

Australia↗
PubMed2001

Divergent replication kinetics of two phenotypically different parvoviruses of rats.

Rat virus (RV) is an important infectious agent of laboratory rats because of its high prevalence and capacity to disrupt research. Additionally, RV infection serves as a model for characterizing virus-host interactions during acute, persistent and prenatal infection. Our research has examined the pathogenesis of two RV strains, RV-UMass and RV-Y. RV-UMass is more pathogenic, causes a higher level of persistent infection and transmits to the foetus after oronasal inoculation of the pregnant dam. To determine in vitro distinctions between the strains that may account for these differences and to provide a benchmark for characterizing virus replication in vivo, synchronized in vitro replication of both RV strains was defined and compared. The results demonstrated that RV replication has replicative intermediates, virus transcripts and proteins similar to those reported for the prototype parvovirus, minute virus of mice. However, the replicative cycle of RV-UMass was 12 h compared with 24 h for RV-Y, and RV-UMass and RV-Y differed in kinetics of virus DNA replication, transcription and protein accumulation. Additionally, in situ analysis correlated well with kinetics data as determined by Southern and Northern blot analysis. Sequence comparisons between the strains also determined coding differences that may contribute to phenotypic differences.

Animals↗